Asymmetric Nucleophilic Catalysis Project Summary: This program will explore the development of enantioselective processes catalyzed by planar-chiral derivatives of 4-(dimethylamino)pyridine (DMAP) and by chiral phosphines. The investigation will focus primarily on their application as nucleophilic catalysts; in addition, a recently discovered dimension of the chemistry of the DMAP derivatives, their use (in protonated form) as Bronsted acid catalysts, will be pursued. A diverse array of reactions (e.g., Staudinger synthesis of beta-lactams, kinetic resolutions of alcohols and amines, annulations, and halogenations) will be examined. Achieving the objectives of this program will facilitate access to important families of compounds in highly enantioenriched form. Relevance: Due to the "handedness" of the molecules of life (proteins, DMA, RNA, sugars, etc.), the two mirror- image versions ("enantiomers") of a particular compound often display quite different biological activity. As a result, there is a tremendous need to selectively generate just one of the two mirror-image compounds (nine of the Top 10 pharmaceutical drugs have "handed" active ingredients, seven of which are single-handed (enantiopure)). Enantioselective catalysis, the focus of this research program, is a particularly attractive strategy for achieving this objective.